Hydrochloric Acid → 1-(1-Naphthoyl)-3-(RS)-(4-(4-fluorophenyl)-piperidinyl-1-ethyl)-4-(RS)-(3-thienyl)pyrrolidine

Participants

Reaction Conditions

Reaction Steps

A solution of 0.16 g (0.47 mmol) of 1-(1-naphthoyl)-3-(SR)-formyl-4-(RS)-(3-thienyl)pyrrolidine (Example 88), and 0.085 g (0.47 mmol) of 4-(4-fluorophenyl)-piperidine in 10 mL of benzene was heated to reflux in a flask fitted with a Dean-Stark trap to azeotrope off the water. After 2 h, the benzene was removed by freeze-drying to give a white powder. The residue was redissolved in 6 mL of THF and the solution was cooled to −78° C. To this solution was added 0.56 mL (0.56 mmol) of a 1N solution of HCl in ether. The mixture was warmed to rt and stirred 30 min at rt. The mixture was then cooled to 0° C. and to it was added 1 mL (1.41 mmol) of methyl magnesium bromide (1N in THF). The reaction mixture was warmed to rt and stirred for 3 h at which time it was quenched with water. The reaction mixture was filtered though a thin layer of silica and concentrated. The residue was purified by chomatography (HPLC, Waters RCM 25×100, silica, hexanes: 0.1% iPr2NH in t-butylmethylether, 8:2.25) to give the two isomers of the title compound.

Provenance & Evidence